Table 2.
GIST molecular subtypes and characteristics.
| Alterations | Characteristics | Systemic Therapeutic Options |
|---|---|---|
| KIT Mutations (60–70%) | ||
| Exon 9 (9–10%) | Small or large intestine |
First-line recommended treatment: Less sensitive to imatinib 400 mg/daily dose, with higher responses to 800 mg/daily dose. |
| Exon 11 (60%) | Gastrointestinal tract; Del 557 and 558—more aggressive |
First-line recommended treatment: Imatinib 400 mg/daily dose. |
| Exon 13 (less than 1%) | All sites |
First-line recommended treatment: Imatinib 400 mg/daily dose—sensitivity is low; sensitivity improves with other TKIs such as regorafenib and sunitinib. |
| Exon 17 (less than 1%) | All sites |
First-line recommended treatment: Imatinib 400 mg/daily dose—usually presents primary resistance. Sensitivity improves with other TKIs such as regorafenib and sunitinib. D816V mutation-resistant to all TKIs with the exception of ponatinib, ripretinib, and avapritinib. |
| PDGFRA Mutations (10–15%) | ||
| Exon 12 (up to 2%) | Gastric (15–18%) and small intestine (5–7%). More indolent behavior and favorable prognosis |
First-line recommended treatment: Imatinib 400 mg/daily dose |
| Exon 14 (less than 2%) | ||
| Exon 18 (non-D842V) (1–2%) | ||
| Exon 18 (D842V) (9–10%) |
First-line recommended treatment: Primary resistance to imatinib therapy. Avapritinib is the preferred regimen. Homologous toD816V mutation—resistant to all TKIs with the exception of ponatinib, ripretinib, and avapritinib. |
|
| KIT and PDGFRA wild-type–SDH-competent | ||
| NF1 mutation (1%) | Small intestines and multicentric |
First-line recommended treatment: Typically, insensitive to imatinib; surgery is the primary treatment. Possible clinical efficacy of MEK inhibitors. |
| RAS mutation (rare) | Unknown | Not sensitive to usual TKIs |
| BRAF mutations (4–13%) | Small intestines and variable clinical behavior Phenotypically and morphologically, similar to KIT/PDGFRA-positive GISTs |
First-line recommended treatment: iBRAF ± iMEK. |
| Other mutations (rare) | NTRK translocations—unknown |
First-line recommended treatment: Specific inhibitors. |
| KIT and PDGFRA wild-type–SDH-deficient | ||
|
SDHA, SDHB, SDHC, or SDHD mutations (<3%) Carney–Stratakis syndrome |
Gastric and small intestine Children, adolescents, and young adults; lymph node involvement, indolent disease |
Generally resistant to imatinib; can present sensitivity to anti-angiogenic TKIs |
|
Loss of SDHB expression (<1%) Carney triad | ||